This program is concerned with the isolation and characterization of ribonucleotide reductase from Saccharomyces cerevisiae and with the role of this enzyme in cellular replication. Specific projects to be undertaken include: (a) isolation from yeast of the stable (fraction A) and labile (fraction B) protein components, both of which are required for catalytic activity; (b) to study the mechanism of the enzyme-catalyzed reaction (e.g. the role of sulfhydryl groups, the possible occurrence of nonheme iron in one of the components); (c) the nature of the nucleotide pool in yeast cells and the effect of these materials in regulating activity of the enzyme; (d) the mechanism by which fluorouracil stimulates synthesis of the enzyme; and (e) the mechanism by which enzyme activity is suppressed after completion of DNA synthesis in the cell cycle.